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PDBsum entry 3qqd

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
3qqd
Jmol
Contents
Protein chains
123 a.a.
129 a.a.
Ligands
SO4 ×2
Metals
_ZN ×2
Waters ×188
PDB id:
3qqd
Name: Oxidoreductase
Title: Human sod1 h80r variant, p212121 crystal form
Structure: Superoxide dismutase [cu-zn]. Chain: a. Engineered: yes. Mutation: yes. Superoxide dismutase [cu-zn]. Chain: b. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: sod1. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932.
Resolution:
1.65Å     R-factor:   0.147     R-free:   0.183
Authors: S.V.Seetharaman,D.D.Winkler,A.B.Taylor,X.Cao,L.J.Whitson, P.A.Doucette,J.S.Valentine,V.Schirf,B.Demeler,M.C.Carroll, V.C.Culotta,P.J.Hart
Key ref: S.V.Seetharaman et al. (2010). Disrupted zinc-binding sites in structures of pathogenic SOD1 variants D124V and H80R. Biochemistry, 49, 5714-5725. PubMed id: 20515040 DOI: 10.1021/bi100314n
Date:
15-Feb-11     Release date:   09-Mar-11    
Supersedes: 3h2r
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00441  (SODC_HUMAN) -  Superoxide dismutase [Cu-Zn]
Seq:
Struc:
154 a.a.
123 a.a.*
Protein chain
Pfam   ArchSchema ?
P00441  (SODC_HUMAN) -  Superoxide dismutase [Cu-Zn]
Seq:
Struc:
154 a.a.
128 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.1.15.1.1  - Superoxide dismutase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2 superoxide + 2 H+ = O2 + H2O2
2 × superoxide
+ 2 × H(+)
= O(2)
+ H(2)O(2)
      Cofactor: Fe cation or Mn(2+) or (Zn(2+) and Cu cation)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   17 terms 
  Biological process     reactive oxygen species metabolic process   60 terms 
  Biochemical function     antioxidant activity     12 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/bi100314n Biochemistry 49:5714-5725 (2010)
PubMed id: 20515040  
 
 
Disrupted zinc-binding sites in structures of pathogenic SOD1 variants D124V and H80R.
S.V.Seetharaman, D.D.Winkler, A.B.Taylor, X.Cao, L.J.Whitson, P.A.Doucette, J.S.Valentine, V.Schirf, B.Demeler, M.C.Carroll, V.C.Culotta, P.J.Hart.
 
  ABSTRACT  
 
Mutations in human copper-zinc superoxide dismutase (SOD1) cause an inherited form of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS). Here, we present structures of the pathogenic SOD1 variants D124V and H80R, both of which demonstrate compromised zinc-binding sites. The disruption of the zinc-binding sites in H80R SOD1 leads to conformational changes in loop elements, permitting non-native SOD1-SOD1 interactions that mediate the assembly of these proteins into higher-order filamentous arrays. Analytical ultracentrifugation sedimentation velocity experiments indicate that these SOD1 variants are more prone to monomerization than the wild-type enzyme. Although D124V and H80R SOD1 proteins appear to have fully functional copper-binding sites, inductively coupled plasma mass spectrometery (ICP-MS) and anomalous scattering X-ray diffraction analyses reveal that zinc (not copper) occupies the copper-binding sites in these variants. The absence of copper in these proteins, together with the results of covalent thiol modification experiments in yeast strains with and without the gene encoding the copper chaperone for SOD1 (CCS), suggests that CCS may not fully act on newly translated forms of these polypeptides. Overall, these findings lend support to the hypothesis that immature mutant SOD1 species contribute to toxicity in SOD1-linked ALS.